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In Case You Missed It:

Understanding ductal carcinoma in situ

Most women diagnosed with this noninvasive breast cancer are
alive 10 years later, and better treatments are emerging.

For the 62,000 women who will be diagnosed with ductal carcinoma
in situ (DCIS) this year, the good news is far more important
than the bad. While cancer is never a picnic, DCIS is the
earliest detectable form of the disease. Some news that sounds
"bad" — for instance, that the incidence of DCIS is increasing
faster than that of any other type of breast cancer — is
encouraging news. It means that more breast cancers are being
detected early, while they can be nipped in the bud. Today, with
standard treatment, 10-year survival rates for DCIS are
approaching 100%, and the treatment is usually not too difficult
to tolerate.

What is DCIS?

The name says a lot about the disease. "Ductal" refers to the
site of origin, the tiny ducts that form a network connecting the
milk-producing structures called lobules. "Carcinoma" indicates a
tumor arising in the epithelium, or lining, of the ducts. "In
situ" delivers the good news that the tumor is confined to its
place of origin; it hasn't invaded the surrounding tissue or
metastasized to other body tissues.

The diagnosis of DCIS describes a cluster of cells captured in
the process of evolving from normal tissue to breast cancer. The
journey is thought to begin with a series of genetic changes in
breast cells. At first, these changes stimulate cell growth,
resulting in ductal hyperplasia (an overabundance of normal
cells), which may begin to fill the duct. Then the cells become
distorted and look abnormal under a microscope. At this second
stage of change, called atypical ductal hyperplasia, the cells'
capacity for growth is further increased. DCIS proper is a third
step in the process, in which a cluster of abnormal cells has
filled the duct but hasn't broken through its walls. If it does
breach the walls, it's called invasive breast cancer.

Carcinogenesis, the process by which cancer arises, may not take
place precisely in these orderly steps. However, pathologists
have developed these classifications as indicators of the
progression of the disease.

Anatomy of ductal carcinoma in situ

Ductal carcinoma in situ (DCIS) is an overgrowth of
abnormal cells in the milk ducts of the breast. It starts
with the proliferation of normal cells lining the milk
ducts (ductal hyperplasia); next, the cells within the
duct become abnormal and rapidly multiply (atypical
ductal hyperplasia); finally, abnormal cells fill the
duct (DCIS). Invasive ductal breast cancer occurs when
abnormal cells break out of the milk duct.

Diagnosing DCIS

Like other types of cancer, DCIS is usually diagnosed by a team
of medical professionals (including radiologists, surgeons, and
pathologists), using the following techniques:

Mammography. In a sense, increased use of mammography is
responsible for the increase in DCIS, because it has increased
detection. Confined to the ducts, DCIS tumors are often too small
to cause symptoms or to be felt on a breast exam. Before
mammograms became routine in the late 1970s, DCIS was usually
discovered incidentally during a biopsy or autopsy, and it was
thought to be rare, constituting fewer than 1% of breast cancers.
Today, DCIS is likely to be identified during an annual mammogram
that reveals tiny calcium deposits — microcalcifications — which
appear as lines or clusters on an x-ray image and are sometimes
associated with cancer. As mammography improves, so does the
diagnosis of DCIS. In 2005, the last year for which statistics
are available, DCIS accounted for more than 20% of newly
diagnosed breast cancers.

Magnetic resonance imaging (MRI) is now increasingly used in
breast imaging, but it hasn't yet been found significantly better
than mammography in screening for DCIS.

Biopsy. Once DCIS is suspected, a biopsy is needed to
determine whether cancer is actually present and, if so, the
extent of the disease. These days, biopsies are more likely to be
performed in the radiology suite than in the operating room. In
the most commonly used procedure, stereotactic core biopsy, a
large needle or thin vacuum tube is guided by ultrasound into the
region of the breast containing microcalcifications to take a
tissue sample. However, when mammography has indicated large
areas of microcalcification, a surgical biopsy may be
recommended.

Pathology. Pathologists examine the biopsy sample to
determine how far the tissue has strayed from normal breast
tissue. They look at the structure and arrangement of the cells
under a microscope and may test the sample to determine the
presence of receptors for estrogen and progesterone or
abnormalities in genes associated with cancer.

By considering the features and growth pattern of the cells, they
will characterize the disease as low grade, intermediate grade,
or high grade — a classification that reflects how different the
tumor cells look from normal cells and how quickly the tumor is
likely to grow.

Treating DCIS

The data are limited on treating modern DCIS — which is
identified by screening mammogram instead of being found rarely
in large tumor masses. Until the 1980s, DCIS was routinely
treated in the same way as most invasive cancers — with
mastectomy.

That situation began to change after a large ongoing study, the
National Surgical Adjuvant Breast and Bowel Project (NSABP),
reported in 1983 that women with small invasive tumors who
underwent lumpectomy followed by radiation were just as likely to
survive as the women who underwent mastectomy. Physicians
naturally assumed that the same approach could also work for
patients with DCIS, and that assumption has been confirmed by
large studies from the NSABP and the European Organization for
Research and Treatment of Cancer.

Treatment decisions

Today, the results of mammography and biopsy determine the choice
between mastectomy and lumpectomy. DCIS is never an emergency, so
you can take a few weeks to weigh your options, which include the
following:

Breast-conserving surgery (lumpectomy) is often recommended
when DCIS is limited to one site and the tumor can be removed
with a clear margin — several millimeters — of healthy
tissue.

Radiation therapy is recommended for all women who have had
breast-conserving surgery, because it reduces the chance of
recurrence after surgery from 30% to 15%. The standard
procedure is full-breast radiation administered in a hospital
or center five days a week for five to eight weeks. Newer
approaches are on the way (see "Future directions in DCIS").

Tamoxifen (Nolvadex) may further reduce the recurrence rate.
In a randomized controlled NSABP study reported in 1999,
women who received tamoxifen after surgery and radiation for
DCIS were only half as likely to have a recurrence within
five years, compared with similarly treated women who got a
placebo.

Mastectomy is associated with a 10-year disease-free survival
rate of 98%. It's usually reserved for women who have DCIS in
more than one part of the breast or in cases where removing
the tumor and a margin of healthy tissue around it would
require a disfiguringly large incision. Mastectomy is also
recommended for women who have a recurrence of DCIS or
invasive cancer at the same site. Some women may choose
mastectomy because they want to avoid undergoing radiation,
or because they want to reduce their risk of recurrence to
the lowest level possible.

Because the risk of metastasis is so low, lymph node biopsy
is not required for diagnosing DCIS, and adjuvant
chemotherapy is not necessary in treating it.

Lobular carcinoma in situ, the other preinvasive disease

Despite its name, lobular carcinoma in situ (LCIS)
technically isn't breast cancer, and it may not even be a
precancerous condition. However, it is generally
considered a risk factor for the disease. Although a
handful of small studies (most including fewer than 200
women) have suggested that LCIS doesn't directly progress
to invasive cancer, women with LCIS are four times more
likely than average to develop invasive ductal cancer and
18 times more likely to develop invasive lobular cancer.

LCIS is a proliferation of abnormal cells in the
milk-producing structures (lobules) of the breast. The
incidence of LCIS has been rising steadily since the late
1980s, mostly among women ages 50 and over. And since
2000, incidence has increased only among those ages 50 to
69 — the group most likely to have regular mammograms.

LCIS doesn't produce lumps that can be felt during breast
exams or microcalcifications that appear on a radiology
screen. It's usually discovered by chance during a biopsy
for a benign breast condition or an invasive form of
cancer. It occurs in an estimated 0.5% to 3.8% of benign
breast biopsies, but no one knows for certain how common
it really is.

LCIS usually arises in several lobules of both breasts,
so lumpectomy isn't an option. Instead, LCIS is managed
in these ways:

Observation. Because LCIS is a
continuing risk factor for cancer, regular breast
exams and annual mammograms are a lifelong must. The
aim is not to find additional LCIS but rather to
detect any developing cancers at the earliest
possible stage. MRI, which is recommended for women
at high risk for breast cancer, is an increasingly
promising option for following women with LCIS.

Preventive measures. Clinicians
recommend either tamoxifen, which reduced cancer
incidence in women with LCIS by as much as 56% in
clinical trials, or a related medication, raloxifene.
Bilateral mastectomy is not routinely recommended,
although it may be considered in women with LCIS who
have factors that significantly increase the risk for
invasive breast cancer, such as the presence of a
BRCA gene mutation.

Future directions in DCIS

DCIS research is directed mainly at improving treatment and,
above all, at preventing progression to invasive disease. As
researchers continue to study the pathology of DCIS, they are
finding that certain tumor characteristics help predict the
treatment most likely to reduce the chance of recurrence. For
example, some forms of breast cancer require estrogen in order to
grow; tumors that do are termed estrogen receptor–positive
(ER-positive). Tamoxifen belongs to a class of drugs called
selective estrogen-receptor modulators (SERMs), which act by
blocking estrogen receptors. Tamoxifen is more likely to prevent
a recurrence in women with ER-positive DCIS than in women with
ER-negative disease.

The use of aromatase inhibitors, which block estrogen production
in the peripheral tissues and breast tissue, is being
investigated in a trial of postmenopausal women with ER-positive
DCIS. For women whose DCIS is ER-negative but who have the
HER-2/neu gene, researchers are exploring the use of trastuzumab
(Herceptin) and lapatinib (Tykerb), which block the tumor growth
factors produced by that gene.

Another promising area of investigation involves the short-term
use of chemotherapy between diagnosis and surgery to alter the
DCIS, so that tissue from the surgical resection can be used by
researchers to assess molecular as well as pathologic evidence of
response. Agents that can induce responses in the "right
direction" — for example, slow or stop the growth of abnormal
cells — may then be further evaluated for their potential in
treatment or prevention.

A new way to administer radiation that is showing some promise in
clinical trials is accelerated partial breast irradiation, in
which the tumor site alone is treated for five days with a
lighter dose of radiation. In another approach, intraoperative
radiation therapy, a one-time dose of radiation is delivered to
the involved area of the breast after the tumor has been removed
but before the incision is closed.

The good news about DCIS

DCIS is sometimes classified as Stage 0 of breast cancer, the
earliest stage of the disease. The question for women with this
diagnosis is not "Will I live?" but "How much treatment will I
need?" One of the biggest risks today is overtreatment. That,
too, is changing, as researchers get better at distinguishing the
types of tumors that can be subdued without extensive surgery or
radiation. DCIS is one cancer that can truly be considered
curable.

If you have DCIS, you might consider entering a clinical trial.
You would get the best available care and might benefit from a
new type of therapy or approach. At the very least, you would be
contributing to much-needed knowledge about this condition. Check
the National Cancer Institute's registry of clinical trials at
www.cancer.gov/clinicaltrials
for a site near you.

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Know your BMI

BMI stands for "body mass index." It's a measure of weight that includes height. A healthy BMI is between 18 and 25. If yours is above 25, losing weight is a good idea. You can calculate your BMI at health.harvard.edu/BMI.